Prostate cancer is a common, but complex disease. Risk factors for this disease are not yet fully understood, but may involve both genetic and environmental influences. These factors may act alone, or in combination, to increase risk of prostate cancer. Some of the most promising potential risk factors are those involved with androgen metabolism, which drives prostate cell growth and differentiation. Therefore, in the following specific aims we propose an epidemiologic study of the relation between prostate cancer and two factors that may affect the androgen metabolism pathway: candidate genes and dietary fat. Specific Aim 1. Our first aim is to investigate the impact of novel or little studied polymorphisms in the following ten androgen pathway candidate genes on prostate cancer risk: 1) CYP3A4; 2) 5a-reductase II; 3) CYP1 7; 4) the Androgen Receptor; 5) Kallikrein 3; 6) 3Beta-hydroxysteroid dehydrogenase II; 7) CYP1 la; 8) CYP19; 9) Insulin-like Growth Factor-I; and 10) CYP1B1 Specific Aim 2. This aim will expand our consideration of the androgen pathway by investigating the relation between prostate cancer risk and consumption of polyunsaturated dietary fat, and the polyunsaturated fatty acids linoleic acid and alpha-linoleic acid. Specific Aim 3. Our third aim is to synthesize the information on candidate genes and dietary fats studied here by looking at their joint and interactive effects on prostate cancer risk. We will use both a conventional analysis, and a hierarchical modeling approach, which will attempt to improve our estimates of risk by incorporating into the analysis biologic information about the affect of these candidate genes and dietary fat on the androgen pathway. To fulfill these specific aims, we will use existing information from a sibling-based study of 455 cases and 488 controls Our comprehensive evaluation of androgen pathway factors should help clarify the impact of these genetic and dietary factors on prostate cancer. Ultimately, findings from such work will help lead to individualized screening that expressly reflects a man's risk of prostate cancer.